Principal Investigator

Liangyi Chen
Super-resolution microscopy, two-photon microscopy, lightsheet microscopy; Single cell organelle interactome; Neuronal circuits in the whole zebrafish brain


Research Interests:

My lab mainly focuses on three interweaved directions: first, we want to continue develop state-of-the-art imaging technologies. At cellular level, we will focus on making live cell superresolution microscopy compatible with higher speed 3D imaging, and less phototoxic. At small model animal and organoid level, we want to perfect the large field-of-view two-photon lightsheet microscopy. At mammalian animal such as mice, we want to make the two-photon/three photon microscopes small enough to be used for high resolution neuronal imaging even under freely heaving conditions. Second, based on the terabyte superresolution imaging datasets generated from live cells per day, we are developing automated data compression and segmentation algorithms based on machine learning and deep learning. With the quantitative segmentation of organelle shapes, positions, and dynamics available, we proposed to map the single cell organelle interactome, which can be used to link single cell omics data to the localized, transient activities that drive cellular behaviors. In the end, we want to establish a profiling method to classify and predict cellular status based on parameters derived from 4D organelle interactome obtained in live cells. Finally, we want to use the large field-of-view two-photon lightsheet microscopy to image both single neurons and neuronal circuits within the whole zebrafish brain, and try to explore dynamic changes in neuronal structure and function at different scales during learning and memory.



Selected Publications:

1. Zhao J, Zong W, Zhao Y, Gou D, Liang S, Shen J, Wu Y, Zheng X, Wu R, Wang X, Niu F, Wang A, Zhang Y, Xiong JW, Chen L*, Liu Y*. Elife. 2019 Jan 29;8. pii: e41540

2. Huang X, Fan J, Li L, Liu H, Wu R, Wu Y, Wei L, Mao H, Lal A, Xi P, Tang L, Zhang Y, Liu Y, Tan S*, Chen L*. Fast, long-term super-resolution imaging with Hessian structured illumination microscopy, Nat Biotech., 2018 Jun;36(5):451-459.

3. Zong W, Wu R, Li M, Hu Y, Li Y, Li J, Rong H, Wu H, Xu Y, Lu Y, Jia H, Fan M, Zhou Z, Zhang Y*, Wang A*, Chen L*, Cheng H. Fast High-resolution Miniature Two-photon Microscopy for Brain Imaging in Freely-behaving Mice at the Single-synapse Level. Nat Methods. 2017 Jul;14(7):713-719.

4. Zong W, Zhao J, Chen X, Lin Y, Ren H, Zhang Y, Fan M, Zhou Z, Cheng H, Sun Y*, Chen L*. Large-field high-resolution two-photon digital scanned light-sheet microscopy. Cell Res. 2015, 25(2):254-7.

5. Yuan T, Liu L, Zhang Y, Wei L, Zhao S, Zheng X, Huang X, Boulanger J, Gueudry C, Lu J, Xie L, Du W, Zong W, Yang L, Salamero J, Liu Y*, Chen L*. Diacylglycerol Guides the Hopping of Clathrin-Coated Pits along Microtubules for Exo-Endocytosis Coupling. Dev Cell. 2015, 35(1):120-30.

6.  Ji W, Xu P, Li Z, Lu J, Liu L, Zhan Y, Chen Y, Hille B*, Xu T*, Chen L*. Functional stoichiometry of the unitary calcium-release-activated calcium channel. Proc Natl Acad Sci U S A. 2008, 105(36):13668-73.



Lab Website: